Aplastic anemia is a condition that involves a low level of red blood cells (anemia), white
blood cells, and platelets without evidence of another bone marrow disease. Anemia leads to
fatigue, shortness of breath, and heart problems. Low platelet counts can lead to bruising
and bleeding, and low white blood cell counts may cause an increased risk of infection,
including pneumonia. Some of the treatment for AA includes transfusion, antibiotics and a
combination of anti-thymocyte globulin (ATG) and cyclosporine with or without steroids, and
growth factors such as G-CSF. For those who are eligible and have a donor, stem cell/bone
marrow transplantation may be used.

MDS is a bone marrow disorder that usually affects older adults. Treatment of the bone
marrow failure that accompanies MDS is usually with supportive care with red blood cell and
platelet transfusions, antibiotics, and combinations of hematopoietic growth factors, which
may partially improve blood cell counts.

It is often difficult to distinguish the hypoplastic variety of MDS from severe AA because
both can result in bone marrow tests with very low cell count numbers. Earlier studies have
shown that in some patients with the hypoplastic MDS, low blood counts respond to
immunosuppressive treatment with ATG and cyclosporine. ATG is made from horse plasma.
Thymoglobulin is a type of ATG made from rabbit plasma. Thymoglobulin has been successfully
used to treat patients with AA who were previously treated with horse ATG but whose disease
has returned. G-CSF is a growth factor that helps raise the white cell count after
receiving chemotherapy. Methylprednisolone is a steroid that is commonly used in treating a
number of medical conditions associated with people's abnormal immune response against
themselves.

If you are found to be eligible to take part in this study, you will receive a combination
of thymoglobulin, cyclosporine, G-CSF, and methylprednisolone. Treatment will be with
thymoglobulin, which will be dosed depending on your age and weight. It will be given by
vein over several hours once a day for a total of 5 days. You will receive the steroid
methylprednisolone by vein before each dose of thymoglobulin to decrease the risk of
developing allergic reactions to thymoglobulin. After 5 days of receiving methylprednisolone
by vein, you will start taking it by mouth once a day at a decreasing dose over about 3
weeks.

The first 5 days of treatment will be given at M. D. Anderson but you will treated outside
the hospital for the rest of the time unless complications develop.

You will be started on cyclosporine as well as G-CSF after completion of thymoglobulin. You
will take cyclosporine by mouth twice a day for 6 months. Your physician may continue
cyclosporine longer at his discretion. You will receive G-CSF as an injection under the skin
for 3 months (or longer) once a day at the discretion of the treating physician starting at
the same time as cyclosporine is started.

You will also receive antibiotic pills to help decrease the risk of infection. You will take
levofloxacin, valacyclovir, fluconazole, or a similar antibiotic by mouth every day for the
length of the study or until your treating physician finds appropriate.

If you have a history of heart disease and you take aspirin for this, your treating
physician may consider stopping the aspirin because of your low platelet count as a result
of your disease. This may increase your risk of heart attacks.

You will have blood tests (about 2 tablespoons each) once or twice a week for the first
month and then once every 2-4 weeks until the end of the study to check if your blood counts
are improving. The level of cyclosporine in your blood will also be checked at these times.
It will require about 1 tablespoon for each of these tests. Monitoring of cyclosporine
levels is a routine test done on all patients who receive this drug in order to avoid toxic
blood levels and side effects.

At about 3 months, you will have a repeat bone marrow biopsy and aspiration as well as blood
tests (about 3 tablespoons) to evaluate your response to the treatment.

You will continue cyclosporine for about 6 months (or longer if your doctor feels that it is
in your interest) and will receive G-CSF for up to about 3 months (or longer if in your
interest). If you develop serious side effects or if the disease gets worse at any time you
will be taken off the study.

At the time when your doctor feels you have had the best possible response to the treatment
and you are coming off study, blood tests (about 3 tablespoons) will be repeated.

Your doctor will continue to remain in touch with you to ensure that your disease remains
under control. This may be done by arranging follow-up visits or through phone or other
means of communication.

This is an investigational study. All the drugs used in this study are FDA approved and
commercially available. Their use together in this study is experimental. A total of 60
patients will take part in this study. All will be enrolled at M. D. Anderson.

Inclusion Criteria:

- Diagnosis of severe aplastic anemia (bone marrow cellularity < 30%, with two of three
peripheral counts at the time of initial presentation or currently low with absolute
neutrophil count (ANC) < 500/mL, pre-transfusion platelet (PLT) < 20,000/mL, or
pre-transfusion hemoglobin < 8 g/dL and presence of no other underlying disorder.

- Diagnosis of MDS (World Health Organization) with bone marrow cellularity < 30%, with
two of three peripheral counts at the time of initial presentation or currently low
with ANC < 500/mL, pre-transfusion PLT < 20,000/mL, or pre-transfusion hemoglobin < 8
g/dL.

- Patients with MDS who have received prior biological therapy (not chemotherapy) are
eligible. Hypomethylating agents and histone deacetylase inhibitors are considered as
biological therapy.

- Age 15 or greater

- Adequate renal function (creatinine less than or equal to 2.0 mg/dL) unless related
to the disease

- Adequate hepatic function (bilirubin less than or equal to 3.5 mg/dL) unless related
to the disease

- No other investigational therapy in the past 14 days

- Able to sign consent form

- Able to comply with the need for contraception (abstinence, condom, birth control
pill, or other acceptable form of contraception) during the entire study period

- Diagnosis of MDS (WHO) with bone marrow cellularity greater than 30%, with low or
intermediate-1 risk by the International Prognostic Scoring System (IPSS) score, and
requiring treatment (i.e. transfusion-dependent)

Exclusion Criteria:

- Active and uncontrolled infection

- HIV positive test

- Pregnant or breast feeding

- Active and uncontrolled medical illness (pulmonary, cardiac, neurological, or other)
that in the opinion of treating physician would likely interfere with study treatment

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